IBPA_HISS2
ID IBPA_HISS2 Reviewed; 4095 AA.
AC Q06277; B0UUL0; Q7WZI3;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 2.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Protein adenylyltransferase and cysteine protease IbpA;
DE Short=HMW IgBP;
DE AltName: Full=p120;
DE Includes:
DE RecName: Full=Protein adenylyltransferase IbpA;
DE EC=2.7.7.n1 {ECO:0000269|PubMed:19362538, ECO:0000269|PubMed:20622875};
DE AltName: Full=AMPylator IbpA;
DE Includes:
DE RecName: Full=Cysteine protease IbpA;
DE EC=3.4.22.-;
DE Contains:
DE RecName: Full=Protein p76 IgBP;
DE AltName: Full=76 kDa antigen;
DE Flags: Precursor;
GN Name=ibpA; Synonyms=p76; OrderedLocusNames=HSM_1489;
OS Histophilus somni (strain 2336) (Haemophilus somnus).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales;
OC Pasteurellaceae; Histophilus.
OX NCBI_TaxID=228400;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION,
RP IMMUNOGLOBULIN-BINDING OF SUBFRAGMENTS, AND IDENTIFICATION OF FULL LENGTH
RP GENE.
RX PubMed=16169703; DOI=10.1016/j.micpath.2005.08.002;
RA Tagawa Y., Sanders J.D., Uchida I., Bastida-Corcuera F.D., Kawashima K.,
RA Corbeil L.B.;
RT "Genetic and functional analysis of Haemophilus somnus high molecular
RT weight-immunoglobulin binding proteins.";
RL Microb. Pathog. 39:159-170(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 2612-4095.
RX PubMed=8245839; DOI=10.1099/00221287-139-9-2135;
RA Cole S.P., Guiney D.G., Corbeil L.B.;
RT "Molecular analysis of a gene encoding a serum-resistance-associated 76 kDa
RT surface antigen of Haemophilus somnus.";
RL J. Gen. Microbiol. 139:2135-2143(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=2336;
RG US DOE Joint Genome Institute;
RA Siddaramappa S., Duncan A.J., Challacombe J.F., Rainey D., Gillaspy A.F.,
RA Carson M., Gipson J., Gipson M., Bruce D., Detter J.C., Han C.S., Land M.,
RA Tapia R., Thompson L.S., Orvis J., Zaitshik J., Barnes G., Brettin T.S.,
RA Dyer D.W., Inzana T.J.;
RT "Complete sequence of Haemophilus somnus 2336.";
RL Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION OF P76, AND IMMUNOGLOBULIN-BINDING.
RC STRAIN=2336, and 649;
RX PubMed=9317034; DOI=10.1128/iai.65.10.4250-4257.1997;
RA Corbeil L.B., Bastida-Corcuera F.D., Beveridge T.J.;
RT "Haemophilus somnus immunoglobulin binding proteins and surface fibrils.";
RL Infect. Immun. 65:4250-4257(1997).
RN [5]
RP FUNCTION, AND OTHER START SITES POSSIBLE.
RC STRAIN=8025;
RX PubMed=12631474; DOI=10.1016/s0882-4010(02)00188-2;
RA Sanders J.D., Bastida-Corcuera F.D., Arnold K.F., Wunderlich A.C.,
RA Corbeil L.B.;
RT "Genetic manipulation of immunoglobulin binding proteins of Haemophilus
RT somnus.";
RL Microb. Pathog. 34:131-139(2003).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-3717; ASN-3723;
RP ARG-3725 AND ARG-3728.
RX PubMed=19362538; DOI=10.1016/j.molcel.2009.03.008;
RA Worby C.A., Mattoo S., Kruger R.P., Corbeil L.B., Koller A., Mendez J.C.,
RA Zekarias B., Lazar C., Dixon J.E.;
RT "The fic domain: regulation of cell signaling by adenylylation.";
RL Mol. Cell 34:93-103(2009).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 3488-3786 OF MUTANT HIS-3717 IN
RP COMPLEX WITH AMPYLATED CDC42, FUNCTION, CATALYTIC ACTIVITY, REACTION
RP MECHANISM, AND MUTAGENESIS OF 3535-ILE-PRO-3536; 3552-ILE-LEU-3553;
RP 3668-LEU--LYS-3670; HIS-3717 AND GLY-3724.
RX PubMed=20622875; DOI=10.1038/nsmb.1867;
RA Xiao J., Worby C.A., Mattoo S., Sankaran B., Dixon J.E.;
RT "Structural basis of Fic-mediated adenylylation.";
RL Nat. Struct. Mol. Biol. 17:1004-1010(2010).
CC -!- FUNCTION: Adenylyltransferase involved in virulence by mediating the
CC addition of adenosine 5'-monophosphate (AMP) to specific tyrosine
CC residue of host Rho GTPases RhoA, Rac and Cdc42. The resulting
CC AMPylation inactivates Rho GTPases, thereby inhibiting actin assembly
CC in infected cells. Probably also acts as a cysteine protease, which may
CC play a central role after invasion of host cell and in virulence.
CC Possible member (with IbpB) of a 2 partner secretion. Probably able to
CC bind bovine epithelial cells (host cells). May participate in the
CC formation of fibrils at the surface of the bacteria.
CC {ECO:0000269|PubMed:12631474, ECO:0000269|PubMed:19362538,
CC ECO:0000269|PubMed:20622875, ECO:0000269|PubMed:9317034}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = diphosphate + O-(5'-adenylyl)-L-
CC tyrosyl-[protein]; Xref=Rhea:RHEA:54288, Rhea:RHEA-COMP:10136,
CC Rhea:RHEA-COMP:13846, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:46858, ChEBI:CHEBI:83624; EC=2.7.7.n1;
CC Evidence={ECO:0000269|PubMed:19362538, ECO:0000269|PubMed:20622875};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = 3-O-(5'-adenylyl)-L-threonyl-
CC [protein] + diphosphate; Xref=Rhea:RHEA:54292, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:13847, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:138113; EC=2.7.7.n1;
CC Evidence={ECO:0000269|PubMed:19362538, ECO:0000269|PubMed:20622875};
CC -!- SUBUNIT: Immunoglobulin-binding protein. {ECO:0000269|PubMed:20622875}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16169703,
CC ECO:0000269|PubMed:9317034}. Note=High molecular weight-immunoglobulin
CC binding protein IbpA, and probably other shorter forms.
CC -!- SUBCELLULAR LOCATION: [Protein p76 IgBP]: Cell outer membrane
CC {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Extracellular
CC side {ECO:0000305}.
CC -!- DOMAIN: The fido domains mediate the adenylyltransferase activity.
CC -!- DOMAIN: The arm region dictates the ability to recognize Rho family
CC proteins. Leu-3668 and Lys-3670 probably lock the position of Tyr
CC substrate in the correct orientation for modification
CC (PubMed:20622875). {ECO:0000269|PubMed:20622875}.
CC -!- DOMAIN: When associated with Cdc42 target, adopts a conformation that
CC mimicks the GDI-bound state of Rho GTPases.
CC {ECO:0000269|PubMed:20622875}.
CC -!- PTM: The long form of the protein is probably processed, and/or the
CC transcript may be subject to differential translational initiation.
CC -!- MISCELLANEOUS: The reaction mechanisms probably follows a substrate-
CC assisted attack of ATP. According to this model, His-3717 acts by
CC attracting a proton from the Tyr substrate, thereby preparing the Tyr
CC as a nucleophile to attack the alpha-phosphate of ATP. This model is
CC consistent with the observation that hydrolysis of ATP is very slow in
CC the absence of Rho GTPases (PubMed:20622875).
CC {ECO:0000305|PubMed:20622875}.
CC -!- SIMILARITY: In the central section; belongs to the fic family.
CC {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the peptidase C58
CC family. {ECO:0000305}.
CC -!- CAUTION: Was originally [PubMed:8245839] thought to be a 76 kDa
CC immunoglobulin-binding protein; it is now apparent that the gene is
CC much longer but how it is translated and processed is unclear.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC36827.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB087258; BAC78649.1; -; Genomic_DNA.
DR EMBL; L10282; AAC36827.1; ALT_INIT; Unassigned_DNA.
DR EMBL; CP000947; ACA31239.1; -; Genomic_DNA.
DR RefSeq; WP_012340627.1; NC_010519.1.
DR PDB; 3N3U; X-ray; 1.85 A; A=3488-3786.
DR PDB; 4ITR; X-ray; 2.30 A; A/B=3482-3797.
DR PDB; 6SIU; X-ray; 2.49 A; A/B=3483-3797.
DR PDBsum; 3N3U; -.
DR PDBsum; 4ITR; -.
DR PDBsum; 6SIU; -.
DR SMR; Q06277; -.
DR STRING; 228400.HSM_1489; -.
DR PRIDE; Q06277; -.
DR EnsemblBacteria; ACA31239; ACA31239; HSM_1489.
DR KEGG; hsm:HSM_1489; -.
DR HOGENOM; CLU_000190_0_0_6; -.
DR OMA; IKNQNYA; -.
DR OrthoDB; 132791at2; -.
DR EvolutionaryTrace; Q06277; -.
DR GO; GO:0009279; C:cell outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0070733; F:protein adenylyltransferase activity; IDA:UniProtKB.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0018117; P:protein adenylylation; IDA:UniProtKB.
DR GO; GO:0036211; P:protein modification process; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 1.10.3290.10; -; 2.
DR Gene3D; 2.160.20.10; -; 1.
DR InterPro; IPR024973; ESPR.
DR InterPro; IPR003812; Fido.
DR InterPro; IPR036597; Fido-like_dom_sf.
DR InterPro; IPR040198; Fido_containing.
DR InterPro; IPR008638; Filamn_hemagglutn_N.
DR InterPro; IPR025157; Hemagglutinin_rpt.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR012334; Pectin_lyas_fold.
DR InterPro; IPR011050; Pectin_lyase_fold/virulence.
DR InterPro; IPR003951; Peptidase_C58.
DR InterPro; IPR006473; Peptidase_C58_Yopt.
DR PANTHER; PTHR13504; PTHR13504; 2.
DR Pfam; PF13018; ESPR; 1.
DR Pfam; PF02661; Fic; 2.
DR Pfam; PF13332; Fil_haemagg_2; 1.
DR Pfam; PF05860; Haemagg_act; 1.
DR Pfam; PF03543; Peptidase_C58; 1.
DR PRINTS; PR01376; BACSURFANTGN.
DR SMART; SM00912; Haemagg_act; 1.
DR SUPFAM; SSF140931; SSF140931; 2.
DR SUPFAM; SSF51126; SSF51126; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR TIGRFAMs; TIGR01901; adhes_NPXG; 1.
DR TIGRFAMs; TIGR01586; yopT_cys_prot; 1.
DR PROSITE; PS51459; FIDO; 2.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell outer membrane; Coiled coil; Hydrolase;
KW Membrane; Multifunctional enzyme; Nucleotide-binding;
KW Nucleotidyltransferase; Protease; Repeat; Secreted; Signal; Thiol protease;
KW Transferase; Virulence.
FT SIGNAL 1..97
FT /evidence="ECO:0000255"
FT CHAIN 98..4095
FT /note="Protein adenylyltransferase and cysteine protease
FT IbpA"
FT /id="PRO_0000338408"
FT CHAIN 3222..4095
FT /note="Protein p76 IgBP"
FT /id="PRO_0000192510"
FT REPEAT 2250..2271
FT /note="1"
FT REPEAT 2272..2295
FT /note="2"
FT REPEAT 2296..2317
FT /note="3"
FT REPEAT 2318..2343
FT /note="4"
FT REPEAT 2344..2365
FT /note="5"
FT REPEAT 2366..2387
FT /note="6"
FT REPEAT 2388..2413
FT /note="7"
FT REPEAT 2414..2435
FT /note="8"
FT REPEAT 2436..2457
FT /note="9"
FT REPEAT 2458..2483
FT /note="10"
FT REPEAT 2484..2505
FT /note="11"
FT REPEAT 2506..2527
FT /note="12"
FT DOMAIN 3218..3355
FT /note="Fido 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00791"
FT DOMAIN 3640..3777
FT /note="Fido 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00791"
FT REGION 972..1515
FT /note="Binds bovine IgG2 Fc"
FT REGION 1082..1117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1116..1255
FT /note="Binds bovine IgG2 Fc"
FT REGION 1130..1154
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1204..1223
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1625..1652
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1705..1732
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2250..2527
FT /note="12 X 22 AA approximate repeats"
FT REGION 2592..2617
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2765..2809
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2825..2894
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2914..2933
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2943..3033
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3049..3069
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3222..4095
FT /note="yopT-like"
FT REGION 3354..3698
FT /note="Binds bovine IgG2 Fc"
FT REGION 3357..3415
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3432..3454
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3535..3557
FT /note="Arm region"
FT REGION 3783..3829
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1116..1247
FT /evidence="ECO:0000255"
FT COMPBIAS 1094..1117
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1139..1153
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1636..1652
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2592..2613
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2772..2803
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2977..3025
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3052..3069
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3361..3400
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3439..3454
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3783..3800
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3801..3829
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 3910
FT /note="For cysteine protease activity"
FT /evidence="ECO:0000255"
FT ACT_SITE 4033
FT /note="For cysteine protease activity"
FT /evidence="ECO:0000255"
FT ACT_SITE 4048
FT /note="For cysteine protease activity"
FT /evidence="ECO:0000255"
FT BINDING 3670..3671
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 3722..3724
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 3728
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 3757
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MUTAGEN 3535..3536
FT /note="IP->AA: Reduced adenylyltransferase toward Rho
FT GTPase family proteins."
FT /evidence="ECO:0000269|PubMed:20622875"
FT MUTAGEN 3552..3553
FT /note="IL->AA: Reduced adenylyltransferase toward Rho
FT GTPase family proteins."
FT /evidence="ECO:0000269|PubMed:20622875"
FT MUTAGEN 3668..3670
FT /note="LTK->ATA: Reduced adenylyltransferase activity."
FT /evidence="ECO:0000269|PubMed:20622875"
FT MUTAGEN 3717
FT /note="H->A: Abolishes adenylyltransferase activity."
FT /evidence="ECO:0000269|PubMed:19362538,
FT ECO:0000269|PubMed:20622875"
FT MUTAGEN 3723
FT /note="N->A: Does not affect adenylyltransferase activity."
FT /evidence="ECO:0000269|PubMed:19362538"
FT MUTAGEN 3724
FT /note="G->A: Nucleotide-binding mutant. No
FT adenylyltransferase activity abd reduced toxicity."
FT /evidence="ECO:0000269|PubMed:20622875"
FT MUTAGEN 3725
FT /note="R->A: Does not affect adenylyltransferase activity."
FT /evidence="ECO:0000269|PubMed:19362538"
FT MUTAGEN 3728
FT /note="R->A: Does not affect adenylyltransferase activity."
FT /evidence="ECO:0000269|PubMed:19362538"
FT HELIX 3499..3511
FT /evidence="ECO:0007829|PDB:3N3U"
FT HELIX 3513..3516
FT /evidence="ECO:0007829|PDB:3N3U"
FT TURN 3517..3519
FT /evidence="ECO:0007829|PDB:3N3U"
FT HELIX 3521..3534
FT /evidence="ECO:0007829|PDB:3N3U"
FT HELIX 3539..3543
FT /evidence="ECO:0007829|PDB:3N3U"
FT HELIX 3549..3552
FT /evidence="ECO:0007829|PDB:3N3U"
FT HELIX 3555..3568
FT /evidence="ECO:0007829|PDB:3N3U"
FT HELIX 3574..3585
FT /evidence="ECO:0007829|PDB:3N3U"
FT HELIX 3596..3609
FT /evidence="ECO:0007829|PDB:3N3U"
FT HELIX 3612..3616
FT /evidence="ECO:0007829|PDB:3N3U"
FT HELIX 3618..3635
FT /evidence="ECO:0007829|PDB:3N3U"
FT HELIX 3642..3651
FT /evidence="ECO:0007829|PDB:3N3U"
FT STRAND 3668..3670
FT /evidence="ECO:0007829|PDB:4ITR"
FT HELIX 3678..3697
FT /evidence="ECO:0007829|PDB:3N3U"
FT HELIX 3702..3716
FT /evidence="ECO:0007829|PDB:3N3U"
FT STRAND 3719..3721
FT /evidence="ECO:0007829|PDB:3N3U"
FT HELIX 3723..3737
FT /evidence="ECO:0007829|PDB:3N3U"
FT TURN 3748..3750
FT /evidence="ECO:0007829|PDB:3N3U"
FT HELIX 3751..3754
FT /evidence="ECO:0007829|PDB:3N3U"
FT STRAND 3758..3762
FT /evidence="ECO:0007829|PDB:3N3U"
FT HELIX 3767..3779
FT /evidence="ECO:0007829|PDB:3N3U"
FT TURN 3780..3782
FT /evidence="ECO:0007829|PDB:4ITR"
SQ SEQUENCE 4095 AA; 450060 MW; 495723E626D5E7DD CRC64;
MNKNCYKLIF SKTRGCLVPV AECITSAVDS GSSDSVVVSE KTDEEDRQGS IEDYRLSNVC
LSVKTFLNPV SSALCLNWKS VSVLLLSMVA APNFAQSAEE AAKAEKTPKL TEIQNGNDGI
QLETKNQNIG VGAGTTENNH PTKLYKTENN VIVIDIAKPN DKGISDNRFQ KFNIPNGAVF
KNNKDQQRSE LVGYLEGNKN LADKEAKVIL NQVTGSELSQ IKGALEILGT KADLVIANQH
GINLNGVQTI NAGRFVATTS KLIDPNKMEF DVTQGTVTID VNGFATDNLP YLDIVAKKIE
QKGTIGNKEK EKNKTSETEI TFIAGKGKIK YNIENDGKTK LEVQKDSNTS QPSDKEEVAI
TGASTGAMHG KSIKLIVTEQ GAGVKHDGII LSENDIKIES NKGDIDLGDK LQAKNEISLN
NAKRITIANE ITADKSITIT ADDVKLKNNK EASATEEAKL KGKGKLASKK VKVEAKKSLV
LDDETKVVAT DLELKSQTLT NQGRIYGNKV KIDTDKLVNK KEIYAEDNLD ITTKGKTVTV
SVNKDNKRKA DVKEETVADL DVGFENTGTI ESKSKAKLTF KDNTSFVSKG NKFIKAKDEL
TIDAQNVVIS ENDELQTTAR LTINAAGNVV NNGLLASGKT LTINAKQGSI YNEKGILGAR
EQLTLSAKGN NKETEGNIIN GADSLLHSEG KMELDAENTV YNLGNIFAKS DLTVKANELI
NDVKLSGSIT KKSPYSVLNR YRRSDIASHG WHNNDYRLWI NPIEFEKAEV KVEKAGLIRA
EGNFKFEGKK GDNQQDATLT NHGVINVKNT FEAQNAKVVN NMKAYQANLL TEFFKQKQDI
TFNYQPRARL FLSALSGQAE RKFNSLEELF DGLFSEQPIT NSSSYYADNS QAVHLLEEIK
SPTFQKAMTL VFGANWKNED HKKLSQRWKE FKEKQDAHFD YRPTDKAKIL AQRINGKIDE
LKNGSTGGFS ESERITVGQH KFDLSKVEFR SEVNRKENLN NSNVDLSALS DLLSIPNLFV
DNSVQLDKTV DKNIEIDEED EFLLKPHTGE EPDLLNENEL SENGKFLDKL LGEIGEKTYI
REVSDDWERD PDEPDEPDYK TESRLETRDR FDTLPSEVQD KLRQKFNEYK EKAQQKRQAE
ALQAKTKNEQ LQSDLETGYK EEEKRQAKND LEKQAELQQL DQQEKEKLAK EKELQGKINE
EKQQEALAKQ KQEQQKQADA KAKIEEEKRL EEYRKELAKD HQIEEALSKN QFLKEVDDTR
PKVETDPLYR TKLQYINQDE YFGSKYFLNK VGSSTDAGKK VAVIGDNYLE HQLITKSIEK
KVDNHLALKY QVNDAQLVKK LIDNSYFESK ELGLKVGEAL TKEQQNQLKQ DIVWYVKANI
NNKEVLLPQV YFANKTLRDA EKFKGLGDAL IRANEINLKT RDVLNSGTIS GKNIDIEAEN
KIKNRGDILS EESTRLVGHK GIDNTARSFV NGNGDVEVQR ASIRTEGHLH LEADEDSDIN
SKGSDIKGKT GFVKARNFNT TDTHRTEHSV EKGRIFSKKG EILGYRKEST QKAISVGSNT
EFDHVHFAIK NDVNQEGSKI KAKVVTGVVQ GDYNTKAGRN AQQTERYIRL DQEYSSGHIS
GAGFTVSHER DSQNGEKTNI GGASSNTGTG FTLGGSFSET REKETSLTHT NSDLQVDHGI
LHVLKKAEIG GVDINKHKFT GKAVEEDEAK AEQQAKAKAA PDATDNAAQK EEPKFKVLSQ
SEVDDLMTEK SANDLFNKYK KVKEDEGFEL SAKEITSNKQ KDEYHLDSER SVLKFGIETE
GHSAIADAVS HVAKEIVEAQ RGVKQDGTVA LQHISDVANI VTGELVGGSS KFGFERNYET
NKVKETSDIR TKIAGNITLS AHGGNLQLKN VESDANSKLT LQAKRNVDIL DGETTRESTE
RQSRQKFAFG INSGCSVMSG GCNGGVSGSV DGNESFTTEK SVTHNNSLLR AKNLKIAAGK
DLNLISSNIK ADHLDLNIKG KTNIVSKQDS FDRLYRGFDF SASAGAALSS STLVKGNGSF
GAGYTHEVEN RKLLNQQAGI VANRITGQIK DLDLVAAHFI NKDENSGFRV SGNVTSQQLN
DSHHKDGGSV GVSVGINERG ASSFNVRGGR AEQKHYDAVQ KSVISGINLK DNNVTGEIVD
DLSKAKTVTR DDVYASTQFN FEVADLVELG EKAKSKLQSK FSKAVNNDAE QPTTTRISSE
DVVEMVDNPL YGSNADVRKL RTLDEVGEGY STLGDQNANK GRKLPNGSDD IYSLLGKVKV
SGDEPVYDKV SAEGAYDLLG DSNANKGRTL RNNSDDLYST VGDANSDISR IRSNVYDEIA
AGPYSLLGRT KAAEEHIYEQ IGEGPYSLLG NGSAVRNRTL GGESNSTYST VGDANSDISR
IRSNVYDEIV AGPYSLLGKP KAAEEHIYEQ IGEGPYSLLG NGSAVRNRTL GGESDSPYST
VGDANSDISR IRSNVYDEIV AGPYSLLGRT KAAEEHIYEQ IGEGPYSLLG NGSAVRNRTL
GGESDSPYSL LGGEGTRNKV LADTIESIYS TLSRPQASSN LEMVDNPLYD SVRRSASDQL
PELPTVRNLL NSDTEAGNGT YSEITSRTRN ANDPLPPLPN EFRTRLSQGA DLADHVYDTI
GSIYSVLSKP KASSNLEMVD NPLYGSVRRA AGDQLPELPT VKTLLNKVEE VGNEIYSEIT
SKTRSANDPL PALPNFRLTQ EVDTADHIYA DINDVVNRAN KAKRDLPATP EATPKVAVDG
GDYATIGEVS PLQPRASRQQ GSSDYEEIPL PQETAPQKTS PVKRTSAEGE DGYATIAEVL
QPRAAKGQVS DYETIPLDEP SQAAVRTERS AVEGDYAEIT SPSIQPRSAR GQSGGEEFEP
FPSEFSSEPQ SPKRALPAEN AVVNELGNEL KARLKSKEDQ ANPAKAEVSE PIYATLDKSP
EGLARAKAKG DEAAAANPIV KTRVEDDVAP ELPARPSNLS DSISNETIAE NGQSVALGTP
KSAVAESNRN NNGNQKLQSE GAEGVSPKTK SEDKSWFAKV KDFFFAKSNK SQAKEAKSEQ
ETVSKPNYDS LEDDLNLKNL LALEDKRGSS FEENVLKNPE FLAEAREIAK KYIPEATIKQ
MGNSPEFDEI LTEGAKKVEK RINDALTFKP SVDEFNEIQG LVKNIQKGSA VDDLNAQTLA
ITEALADTSK TIQRNPKLKE EVQGAIEEFL KSSQGKELTV EMIEKLNHGL RPDEGSDRLL
YKKENLTKEN AVFSSPQASK IQLNETVDFI NQAIKQNVEP SVLAGLVYQR LIAYHPFAEG
NGRMARVVVN KILLDAGYPP FTKFSSEFET QIIPQTKATA KSATSAEVVK EFLTELGKKS
SPQEGGANNQ NGQATSPVTL KSKDVSEVEN TQSADSLTIK QPEQGKAGGQ LPSVPKVETS
VNEVAPLSSV PAELKDAAGG NKKAAEKSEG ATGVEKEKTT LFQRVKQFFT GSKSGAKPVA
GDETANKVNY QDLEDNLNLK GLISLEDDRN ANFESNVLKN EKFLDEAREI SKKSIPEATV
KQMSHLPEFD DILTEGAKKV ESRINKAITF RPSVEEFSEI QDLVKTLPKT KVIEDLSTKT
NEITEALAAT SKTIQRTPEL KEQLKTAIED FLQNSQGKPL TVQMIENLNH GLRPDEGEGR
LLYKKENLTK ENAVFSSPEA AKIQLAETVD FINRAKNEGI EPSVVGALVY QRLIAYHPFA
EGNGRMARVI VNKILLDAGY PAFTKFSDEF EPQIIPQTKA STKSATSSEV VVEFLKELAK
KGSKEDNEQN LEKTDRTSTD LTESAVENSA ALSSGTVRSA TVSETVTETE QAKAKPVSDL
VSSKDLVEQQ RTVLQRIQDQ FQPLKVKSKI DAVRSSVEEF GGEVSFKFAQ SKGEVYKEIV
KHIETQNGVC ESTCAHWIAK NVNPTDENFF NTLYEGGKKG HLKKETIDSI KKLQTEFINS
GSATQQFKLT DSWLQEQGVV PKEKKVADFV RRDEVSGTVS KNDVSSLVKA ILDTGDDTAG
VKKISINLEG GSHTVSAAVD GSKVTFFDPN FGEMTFPTHQ QFENWLKNAF WQKSGYAGKQ
EGRRFFNVVN YKKNN
